Structure and assembly of the Alu domain of the mammalian signal recognition particle

The Alu domain of the mammalian signal recognition particle (SRP) comprises the heterodimer of proteins SRP9 and SRP14 bound to the 5' and 3' terminal sequences of SRP RNA. It retards the ribosomal elongation of signal-peptid e-containing proteins before their engagement with the translocation machin ery in the endoplasmic reticulum. Here we report two crystal structures of the heterodimer SRP9/14 bound either to the 5' domain or to a construct con taining both 5' and 3' domains. We present a model of the complete Alu doma in that is consistent with extensive biochemical data. SRP9/14 binds strong ly to the conserved core of the 5' domain, which forms a U-turn connecting two helical stacks. Reversible docking of the more weakly bound 3' domain m ight be functionally important in the mechanism of translational regulation . The Alu domain structure is probably conserved in other cytoplasmic ribon ucleoprotein particles and retroposition intermediates containing SRP9/14-b ound RNAs transcribed from Alu repeats or related elements in genomic DNA.